These Italian researchers have been at the forefront of biomarker and genetic research in PSP. In this study, they find a certain haplotype to be over-represented in PSP, CBS, and FTD,as compared to healthy controls.
I’m sure this Italian research team is participating in the PSP/CBD genetics project overseen by UPenn. It will be interesting to see if the four new genetic mutations found by the UPenn-led project include this A-G-G haplotype.
Robin
Journal of Alzheimers Disease. 2010 Apr 22. [Epub ahead of print]
VEGF Haplotypes are Associated with Increased Risk to Progressive Supranuclear Palsy and Corticobasal Syndrome.
Borroni B, Del Bo R, Goldwurm S, Archetti S, Bonvicini C, Agosti C, Bigni B, Papetti A, Ghezzi S, Sacilotto G, Pezzoli G, Gennarelli M, Bresolin N, Comi GP, Padovani A.
Centre for Aging Brain and Neurodegenerative Disorders, Department of Neurology, University of Brescia, Brescia, Italy.
Abstract
Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are in the spectrum of tauopathies and recognized to have a strong genetic background. It has been widely reported that MAPT tau haplotype H1 is a genetic risk factor in both conditions, but no other genetic determinants have so far been proposed.
Recently, vascular endothelial growth factor (VEGF) haplotypes were reported to confer risk to frontotemporal dementia (FTD). The aim of this study was to evaluate the role of VEGF genetic determinants in PSP and CBS susceptibility.
We evaluated a cohort of 687 unrelated Italian subjects, including 117 PSP, 108 CBS, 199 FTD, and 263 healthy controls. Genotype and allele frequencies of three well-known polymorphisms located within the VEGF promoter (-2578C/A, -1190G/A, and -1154G/A) were carried out. Genetic analysis revealed the presence of significant changes in terms of genotype and allele distributions in patients compared to healthy controls.
A-G-G haplotype (-2578C/A, 1190G/A, -1154G/A) was overrepresented in both PSP (OR=6.64, 95% CI=2.3-19.6, P=0.0003, CGG=reference) and CBS (OR=5.20, 95% CI=1.70-15.9, P=0.003, CGG=reference) compared to healthy subjects. No differences between PSP and CBS and FTD were found, and the A-G-G haplotype was also overrepresented in FTD.
Overall, these data suggest that VEGF gene variability represents a susceptibility factor for PSP and CBS. These data argue that additional genes may confer disease risk to PSP and CBS, and to FTD as well, beyond the MAPT tau haplotype. Further studies are warranted.
PubMed ID#: 20413880 (see pubmed.gov for abstract only)